Involvement of retrotransposon L1 in stemness and cellular plasticity

Apostolou, Panagiotis; Toloudi, Maria; Chatziioannou, Marina; Kourtidou, Eleni; Georgia, Mimikakou; Vlachou, Ioanna; Chlichlia, Katerina; Papasotiriou, Ioannis

doi:10.3109/15419061.2014.970270

Cited by 8 publications

(8 citation statements)

References 30 publications

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“…It is not unreasonable to think that disruption of these regulatory elements following LINE-1 insertion may induce a transcriptional reprograming involving a variety of genes directly or indirectly controlling cell growth. Consistent with this view is the fact that ORF2p could modulate the expression of genes regulating epithelial to mesenchymal transition or stemness in colon cancer cells (62) and that LINE-1 inhibition induced the expression of endogenous miRNAs targeting tumor-suppressor genes in breast cancer cells (107).…”

Section: Role Of Line-1 In Tumorigenesismentioning

confidence: 91%

“…The mobile nature of retrotransposons and the relatively high degree of evolutionary conservation of these sequences are certainly contributing to genome evolution (61). However, numerous studies have reported experimental evidences showing that these elements can also play a functional role in the regulation of key biological processes at the genetic or epigenetic level including tumorigenesis, though the precise mechanism by which this is occurring is not fully understood yet (55,(62)(63)(64)(65)(66). In normal differentiated tissues, LINE-1 is either not detected or is expressed at very low levels as it is maintained repressed by methylation of its promoter (67)(68)(69).…”

Section: Role Of Line-1 In Tumorigenesismentioning

confidence: 99%

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LINE-1 as a therapeutic target for castration-resistant prostate cancer

Houédé

Piazza

Pourquier³

2018

Front Biosci

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Prostate cancer is the third leading cause of death by cancer in men. Surgery or hormone deprivation usually contains the progression of the local forms of the disease. In metastatic situations, chemotherapy or second generation hormone therapies are used with an overall survival that never exceeds 36 months when tumors become resistant to castration. In the search for new alternatives, clinical trials with various classes of anticancer drugs have been performed, including chemotherapies, targeted therapies with kinase inhibitors, radium-223, or immunotherapies with somehow limited efficacy. Targeting LINE-1 with reverse transcriptase inhibitors was also proposed as an attractive strategy as retrotransposons may play a role in the initiation and the progression of prostate cancers. After reviewing the biological rational to use RT inhibitors in the treatment of prostate cancers, we will discuss the results of the phase II trial evaluating the efficacy of Efavirenz in the treatment of castration-resistant prostate cancers with a particular emphasis on pharmacokinetics data that were obtained. We will also discuss the positioning of other RT inhibitors in the current therapeutic armamentarium.

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Section: Role Of Line-1 In Tumorigenesismentioning

confidence: 91%

Section: Role Of Line-1 In Tumorigenesismentioning

confidence: 99%

LINE-1 as a therapeutic target for castration-resistant prostate cancer

Houédé

Piazza

Pourquier³

2018

Front Biosci

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“…In melanoma, expression of HERV‐K retrotransposons induces a stem cell‐like change that is characterized by higher levels of cell migration and invasion . This retrotransposon‐induced phenotype change has also been documented in the epithelial to mesenchymal transition process, which is deleterious in cancer cells as it can promote cell invasion and metastasis …”

Section: Rdgs May Regulate the Shared Features Of Placental And Camentioning

confidence: 96%

The Genes of Life and Death: A Potential Role for Placental‐Specific Genes in Cancer

et al. 2017

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The placenta invades the adjacent uterus and controls the maternal immune system, like a cancer invades surrounding organs and suppresses the local immune response. Intriguingly, placental and cancer cells are globally hypomethylated and share an epigenetic phenomenon that is not well understood - they fail to silence repetitive DNA sequences (retrotransposons) that are silenced (methylated) in healthy somatic cells. In the placenta, hypomethylation of retrotransposons has facilitated the evolution of new genes essential for placental function. In cancer, hypomethylation is thought to contribute to activation of oncogenes, genomic instability, and retrotransposon unsilencing; the latter, we postulate, is possibly the most important consequence. Activation of placental retrotransposon-derived genes in cancer underpins our hypothesis that hypomethylation of these genes drives cancer cell invasion. This alludes to an interesting paradox, that while placental retrotransposon-derived genes are essential for promoting early hominid life, the same genes promote disease-susceptibility and death through cancer.

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“…The most abundant RNA transposons in the human genome are LINEs (Long INterspersed Elements; about 20%) and SINEs (Short INterspersed Elements; about 13%) (Ayarpadikannan and Kim, 2014). LINE-1, which only has 100 active copies per human genome (Xiao-Jie et al, 2016), can serve as a prognostic factor of cancer progress, and even as a therapeutic target (Apostolou et al, 2015). In contrast, SINEs are non-autonomous since they do not encode proteins and require LINE-coded proteins for their propagation.…”

Section: Introductionmentioning

confidence: 99%

Peer Review #2 of "Biomarker potential of repetitive-element transcriptome in lung cancer (v0.2)"

Feng¹

2019

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Since repetitive elements (REs) account for nearly 53% of the human genome, profiling its transcription after an oncogenic change might help in the search for new biomarkers. Lung cancer was selected as target since it is the most frequent cause of cancer death. A bioinformatic workflow based on well-established bioinformatic tools (such as RepEnrich, RepBase, SAMTools, edgeR and DESeq2) has been developed to identify differentially expressed RNAs from REs. It was trained and tested with public RNA-seq data from matched sequencing of tumour and healthy lung tissues from the same patient to reveal differential expression within the RE transcriptome. Healthy lung tissues express a specific set of REs whose expression, after an oncogenic process, is strictly and specifically changed. Discrete sets of differentially expressed REs were found for lung adenocarcinoma, for small-cell lung cancer, and for both cancers. Differential expression affects more HERV-than LINE-derived REs and seems biased towards down-regulation in cancer cells. REs behaving consistently in all patients were tested in a different patient cohort to validate the proposed biomarkers. Down-regulation of AluYg6 and LTR18B was confirmed as potential lung cancer biomarkers, while up-regulation of HERVK11D-Int is specific for lung adenocarcinoma and up-regulation of UCON88 is specific for small cell lung cancer. Hence, the study of RE transcriptome might be considered another research target in cancer, making REs a promising source of lung cancer biomarkers.

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Involvement of retrotransposon L1 in stemness and cellular plasticity

Cited by 8 publications

References 30 publications

LINE-1 as a therapeutic target for castration-resistant prostate cancer

LINE-1 as a therapeutic target for castration-resistant prostate cancer

The Genes of Life and Death: A Potential Role for Placental‐Specific Genes in Cancer

Peer Review #2 of "Biomarker potential of repetitive-element transcriptome in lung cancer (v0.2)"

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